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GeneBe

rs4561

Positions:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001118890.2(GLRX):ā€‹c.225T>Cā€‹(p.Ile75=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,580,096 control chromosomes in the GnomAD database, including 125,296 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.37 ( 10776 hom., cov: 31)
Exomes š‘“: 0.40 ( 114520 hom. )

Consequence

GLRX
NM_001118890.2 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.15
Variant links:
Genes affected
GLRX (HGNC:4330): (glutaredoxin) This gene encodes a member of the glutaredoxin family. The encoded protein is a cytoplasmic enzyme catalyzing the reversible reduction of glutathione-protein mixed disulfides. This enzyme highly contributes to the antioxidant defense system. It is crucial for several signalling pathways by controlling the S-glutathionylation status of signalling mediators. It is involved in beta-amyloid toxicity and Alzheimer's disease. Multiple alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Aug 2011]
RHOBTB3 (HGNC:18757): (Rho related BTB domain containing 3) Enables ATP binding activity and small GTPase binding activity. Involved in retrograde transport, endosome to Golgi. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.14 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GLRXNM_001118890.2 linkuse as main transcriptc.225T>C p.Ile75= synonymous_variant 2/3 ENST00000237858.11
GLRXNM_001243658.2 linkuse as main transcriptc.225T>C p.Ile75= synonymous_variant 2/3
GLRXNM_001243659.2 linkuse as main transcriptc.225T>C p.Ile75= synonymous_variant 2/3
GLRXNM_002064.3 linkuse as main transcriptc.225T>C p.Ile75= synonymous_variant 2/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GLRXENST00000237858.11 linkuse as main transcriptc.225T>C p.Ile75= synonymous_variant 2/31 NM_001118890.2 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.371
AC:
56350
AN:
151844
Hom.:
10779
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.329
Gnomad AMI
AF:
0.422
Gnomad AMR
AF:
0.310
Gnomad ASJ
AF:
0.419
Gnomad EAS
AF:
0.178
Gnomad SAS
AF:
0.367
Gnomad FIN
AF:
0.374
Gnomad MID
AF:
0.424
Gnomad NFE
AF:
0.421
Gnomad OTH
AF:
0.393
GnomAD3 exomes
AF:
0.363
AC:
91306
AN:
251296
Hom.:
17568
AF XY:
0.373
AC XY:
50684
AN XY:
135826
show subpopulations
Gnomad AFR exome
AF:
0.324
Gnomad AMR exome
AF:
0.222
Gnomad ASJ exome
AF:
0.415
Gnomad EAS exome
AF:
0.181
Gnomad SAS exome
AF:
0.387
Gnomad FIN exome
AF:
0.384
Gnomad NFE exome
AF:
0.425
Gnomad OTH exome
AF:
0.388
GnomAD4 exome
AF:
0.395
AC:
564812
AN:
1428134
Hom.:
114520
Cov.:
26
AF XY:
0.397
AC XY:
282892
AN XY:
712506
show subpopulations
Gnomad4 AFR exome
AF:
0.313
Gnomad4 AMR exome
AF:
0.232
Gnomad4 ASJ exome
AF:
0.412
Gnomad4 EAS exome
AF:
0.162
Gnomad4 SAS exome
AF:
0.387
Gnomad4 FIN exome
AF:
0.386
Gnomad4 NFE exome
AF:
0.414
Gnomad4 OTH exome
AF:
0.387
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.371
AC:
56369
AN:
151962
Hom.:
10776
Cov.:
31
AF XY:
0.367
AC XY:
27291
AN XY:
74266
show subpopulations
Gnomad4 AFR
AF:
0.329
Gnomad4 AMR
AF:
0.310
Gnomad4 ASJ
AF:
0.419
Gnomad4 EAS
AF:
0.179
Gnomad4 SAS
AF:
0.368
Gnomad4 FIN
AF:
0.374
Gnomad4 NFE
AF:
0.421
Gnomad4 OTH
AF:
0.392
Alfa
AF:
0.410
Hom.:
21241
Bravo
AF:
0.363
Asia WGS
AF:
0.264
AC:
919
AN:
3478
EpiCase
AF:
0.433
EpiControl
AF:
0.431

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.096
DANN
Benign
0.49
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4561; hg19: chr5-95152313; COSMIC: COSV52986908; API